Summary

• Indications and Usage: INVEGA TRINZA, a 3-month injection, is indicated for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA (1-month paliperidone palmitate extended-release injectable suspension) for at least four months.¹
• Dosing: Initiate INVEGA TRINZA when the next 1-month paliperidone palmitate dose is scheduled with an INVEGA TRINZA dose based on the previous 1-month injection dose, using the equivalent 3.5-fold higher dose (see Table: INVEGA TRINZA Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA in the Full Prescribing Information). Following the initial INVEGA TRINZA dose, INVEGA TRINZA should be administered every 3 months.¹
• Pharmacokinetic Modeling: Extrapolated pharmacokinetic (PK) simulations were conducted to investigate the optimal frequency of administration of the 819 mg dose of INVEGA TRINZA to attain similar paliperidone exposures to a 234 mg dose of INVEGA SUSTENNA administered every 3 weeks. INVEGA TRINZA 819 mg every 8 weeks appeared to most closely approximate the paliperidone exposures achieved with INVEGA SUSTENNA 234 mg administered every 3 weeks at steady-state. Importantly, these simulations represent extrapolations of a pharmacokinetic model, and have not been investigated in clinical trials.²
• More frequent administration of INVEGA SUSTENNA (e.g., every 3 weeks) or INVEGA TRINZA (e.g., every 8 weeks) is not consistent with the Prescribing Information for either product, and, is therefore, not recommended.
• Other available INVEGA SUSTENNA doses (39, 78, 117, and 156 mg) were not included in the extrapolated PK modeling simulation for this scenario.

PRODUCT LABELING

Please refer to the following section of the Full Prescribing Information¹ that is relevant to your inquiry: DOSAGE AND ADMINISTRATION.

Dose Initiation: Initiate INVEGA TRINZA when the next 1-month paliperidone palmitate dose is scheduled with an INVEGA TRINZA dose based on the previous 1-month injection dose, using the equivalent 3.5-fold higher dose. See Table: INVEGA TRINZA Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA.¹

PK MODELING

Extrapolated PK simulations were developed to investigate the optimal frequency of administration of the 819 mg dose of INVEGA TRINZA to attain similar paliperidone exposures to a 234 mg dose of INVEGA SUSTENNA administered every 3 weeks.² This simulation assessed the paliperidone plasma PK profile when INVEGA SUSTENNA 234 mg was administered every 3 weeks (with the exception of the first three maintenance doses which were every 4 weeks) until steady-state was achieved, and then either INVEGA SUSTENNA 234 mg every 3 weeks was continued, or there was a switch to INVEGA TRINZA 819 mg every 8, 10, or 12 weeks.

By visual examination, INVEGA TRINZA 819 mg every 8 weeks (via deltoid or gluteal injections) appeared to most closely approximate the paliperidone exposures achieved with INVEGA SUSTENNA 234 mg administered every 3 weeks at steady-state (via deltoid or gluteal injections; see Figure: Comparison of INVEGA SUSTENNA 234 mg (Deltoid and Gluteal) Every 3 Weeks at Steady-state and INVEGA SUSTENNA 234 mg Every 3 Weeks at Steady-state Followed by a Switch to 819 mg INVEGA TRINZA Every 8, 10, or 12 Weeks.² In addition, the steady-state minimum paliperidone concentration (C_min) achieved with INVEGA SUSTENNA 234 mg administered every 3 weeks was largely similar to that obtained after the switch to INVEGA TRINZA 819 mg administered every 8 weeks. See Table: Comparison of C_max and C_min for INVEGA SUSTENNA 234 mg (Deltoid and Gluteal) Every 3 Weeks at Steady-state and INVEGA SUSTENNA 234 mg Every 3 Weeks at Steady-state Followed by a Switch to 819 mg INVEGA TRINZA Every 8, 10, or 12 Weeks.

Importantly, these simulations represent extrapolations of a pharmacokinetic model, and have not been investigated in clinical trials. Additionally, more frequent administration of INVEGA SUSTENNA (e.g., every 3 weeks) or INVEGA TRINZA (e.g., every 8 weeks) is not consistent with the Prescribing Information for either product, and, is therefore, not recommended.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 13 May 2024.